ABSTRACT
Background Individual inborn errors of metabolism (IEMs) are rare disorders. Expanded newborn screening for IEMs by tandem mass spectrometry (TMS) is an efficient approach for early diagnosis. Here we provide the newborn screening program for the application of this approach (between July 2014 and March 2019) to the identification of newborns in Beijing at risk of developing a potentially fatal disease. Methods The amino acids and acylcarnitines in dried blood spots were analyzed by TMS. Diagnoses of newborns with elevated metabolites were confirmed by gas chromatography-mass spectrometry, biochemical studies, and genetic analysis. Results Among the healthy newborns, 16 metabolic disorder cases were confirmed, giving a total birth prevalence of 1:3666 live births. Organic acidemia (OA) was the most common (9/16 patients; 56%), and methylmalonic acidemia was the most frequently observed OA (7/9 patients; 89%). Five infants were diagnosed with methylmalonic acidemia with homocystinuria type CblC, two with isolated methylmalonic acidemia, one with propionic acidemia, and one with isovaleric acidemia. Four patients (4/16, 25%) were diagnosed with hyperphenylalaninemia. One suffered with medium-chain acyl CoA dehydrogenase deficiency, one with carnitine uptake deficiency, and one with citrin deficiency. Eleven cases underwent genetic analysis. Seventeen mutations in eight IEM-associated genes were identified in 11 confirmed cases. Symptoms were already present within 2 days after birth in 44% (7/16) cases. The infant with propionic acidemia died at 7 days after birth. The other cases received timely diagnosis and treatment, and most of them grew well. Conclusions The results illustrate challenges encountered in disease management highlighting the importance of newborn screening for inherited metabolic disorders, which is not yet nationally available in our country. Regional newborn screening programs will provide a better estimation of the incidence of IEM.
Subject(s)
Amino Acids/metabolism , Carnitine/analogs & derivatives , Metabolism, Inborn Errors/diagnosis , Tandem Mass Spectrometry/methods , Beijing , Carnitine/metabolism , Female , Humans , Infant, Newborn , Male , Metabolism, Inborn Errors/metabolism , Neonatal ScreeningABSTRACT
BACKGROUND: Cheyne-Stokes respiration with central sleep apnea (CSR-CSA) is very common in patients with chronic congestive heart failure (CHF). A current concept of the key pathophysiological mechanism leading to CSR-CSA is a fluctuation of PaCO2 below and above the apneic threshold. A number of therapeutic approaches for CSR-CSA have been proposed-all with varying success, some of which include various modes of positive airway pressure among other strategies. However, CO2 oscillations seen in CSR-CSA have yet to be looked at as a specific therapeutic target by current treatments. DISCUSSION: Previous studies have shown that delivery of constant CO2 is efficacious in eliminating CSR-CSA by raising PaCO2, but there are serious concerns about the potential side effects, such as unwanted elevations in ventilation, work of breathing, and sympathetic nerve activity (SNA), and consequently CO2 inhalation therapy has not been recommended as a routine option for therapy. However, recent new studies into CO2 inhalation therapy have been made that may reshape its role as therapeutic. In this review, we will focus on the recent developments of administration of dynamic CO2 in the management of CSR-CSA in CHF patients.
